Abstract
Autism Spectrum Disorder (ASD) is currently estimated to impact more than 1% of the population world-wide. Within that population, upwards of 70% of individuals experience moderate to severe gastrointestinal (GI) distress with unspecified cause. Although GI distress has become a well-established co-occurring symptom in autism, the underlying pathophysiology that causes this suite of symptoms remains unexplained. My work addresses this gap in ASD research, which is still primarily focused on the central nervous system (CNS) and diagnostic behavioral criteria while overlooking important GI and microbial contributions to the disorder. Due to the comparatively higher experimental accessibility of monogenic models of ASD, I use zebrafish and focus on two ASD related genes (SHANK3 and SYNGAP1) in an attempt to explain the driving forces behind ASD related GI distress. The studies in this dissertation demonstrate that GI dysfunction is not only a common phenotype in animal models of ASD, but that GI symptoms may also share core mechanisms intrinsic to the gut that reduce intestinal tract motility across multiple genetic forms of ASD. By gaining a better understanding of GI pathophysiology, the long-term goal is to inform a more holistic approach to managing the broad range of symptoms in ASD.